The public, and especially workers in certain industries and trades, are exposed to a variety of toxic metals ("metal" is used for metallic salt). The degree to which mixtures of metals present in the body are synergistic, additive, or antagonistic with respect to "toxicity" is a virtually unexplored area. In addition, the treatment of metal intoxication by a single chelating agent is not always successful and, in fact, numerous instances are cited in which therapy with a single chelant for acute or subacute poisoning by metals harmed the patient. The objectives of the proposed experimental program, using mice, are: (1) To develop improved therapy for intoxication by cadmium, lead, and mercury using mixed chelates and mixed ligand complexes. Different combinations of chelating agents will first be screened for decorporating ability by the quantitative degree to which they enhance the unltrafilterability of the metals from isssue homogenates prepared from animals previously exposed to the metals. Chelants to be tested include those used in currentmedical practice such as BAL, EDTA, and penicillamine; (2) To ascertain, for initial screening purposes, the lethanlity of mixtures of the toxic metals; (3) To determine the clastogenic (chromosome-breaking) properties in vivo in bone-marrow and germ cells following single and repeated exposures of the animals to apparently non-injurious levels of he metals; (4) To evaluate successful mixed chelant for their relative effectiveness on decorporation, lethality, and cytogeneticity of Cd, Hg, and Pb, including the methyl mercuric chloride salt. The metals will be adminsitered by various routes including oral. To expedite analyses, radioactive nuclides of the metals will be employed where feasible. Since blood and urine levels of metals do not necessarily reflect actual body burdens, it is expected that the best mixed chelant formulations can eventually be used as provocative or challenging drugs to identify workers and others having unsuspected, above acceptable levels of toxic metals in the body.